WO2009034453A4 - Method for the immobilization of bioactive molecules within a polymeric substrate resistant to the stomach acids as oral drug delivery system - Google Patents
Method for the immobilization of bioactive molecules within a polymeric substrate resistant to the stomach acids as oral drug delivery system Download PDFInfo
- Publication number
- WO2009034453A4 WO2009034453A4 PCT/IB2008/002368 IB2008002368W WO2009034453A4 WO 2009034453 A4 WO2009034453 A4 WO 2009034453A4 IB 2008002368 W IB2008002368 W IB 2008002368W WO 2009034453 A4 WO2009034453 A4 WO 2009034453A4
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- insulin
- kgy
- bioactive molecules
- orally
- radiation
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract 13
- 230000000975 bioactive effect Effects 0.000 title claims abstract 10
- 239000000758 substrate Substances 0.000 title claims abstract 3
- 238000012377 drug delivery Methods 0.000 title claims 2
- 229940126701 oral medication Drugs 0.000 title claims 2
- 239000002253 acid Substances 0.000 title abstract 3
- 150000007513 acids Chemical class 0.000 title abstract 3
- 210000002784 stomach Anatomy 0.000 title abstract 3
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims abstract 18
- 102000004877 Insulin Human genes 0.000 claims abstract 9
- 108090001061 Insulin Proteins 0.000 claims abstract 9
- 229940125396 insulin Drugs 0.000 claims abstract 9
- 239000000178 monomer Substances 0.000 claims abstract 4
- 239000007864 aqueous solution Substances 0.000 claims abstract 2
- 230000005855 radiation Effects 0.000 claims 7
- 229920000307 polymer substrate Polymers 0.000 claims 4
- 238000011282 treatment Methods 0.000 claims 4
- 239000011159 matrix material Substances 0.000 claims 3
- 229940123457 Free radical scavenger Drugs 0.000 claims 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims 2
- 239000000017 hydrogel Substances 0.000 claims 2
- 239000002516 radical scavenger Substances 0.000 claims 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 2
- 230000005461 Bremsstrahlung Effects 0.000 claims 1
- 150000001252 acrylic acid derivatives Chemical class 0.000 claims 1
- 239000013543 active substance Substances 0.000 claims 1
- 229920001577 copolymer Polymers 0.000 claims 1
- 238000010894 electron beam technology Methods 0.000 claims 1
- 230000008014 freezing Effects 0.000 claims 1
- 238000007710 freezing Methods 0.000 claims 1
- 239000011521 glass Substances 0.000 claims 1
- 235000011187 glycerol Nutrition 0.000 claims 1
- 229920001519 homopolymer Polymers 0.000 claims 1
- 230000001225 therapeutic effect Effects 0.000 claims 1
- 230000005865 ionizing radiation Effects 0.000 abstract 3
- 210000004185 liver Anatomy 0.000 abstract 3
- 229920000642 polymer Polymers 0.000 abstract 3
- 230000003111 delayed effect Effects 0.000 abstract 2
- 239000000203 mixture Substances 0.000 abstract 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 abstract 1
- 230000004888 barrier function Effects 0.000 abstract 1
- 230000004087 circulation Effects 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 abstract 1
- 239000003814 drug Substances 0.000 abstract 1
- 230000000694 effects Effects 0.000 abstract 1
- 230000002496 gastric effect Effects 0.000 abstract 1
- 239000008103 glucose Substances 0.000 abstract 1
- 230000002440 hepatic effect Effects 0.000 abstract 1
- 238000006116 polymerization reaction Methods 0.000 abstract 1
- 230000003252 repetitive effect Effects 0.000 abstract 1
- 230000000979 retarding effect Effects 0.000 abstract 1
- 230000001839 systemic circulation Effects 0.000 abstract 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/28—Insulins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
- A61K9/0092—Hollow drug-filled fibres, tubes of the core-shell type, coated fibres, coated rods, microtubules or nanotubes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Diabetes (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Endocrinology (AREA)
- Zoology (AREA)
- Nanotechnology (AREA)
- Inorganic Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Gastroenterology & Hepatology (AREA)
- Emergency Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
Abstract
It is described a technology which allows to surpass the gastric barrier for proteic compounds administrating bioactive molecules, particularly insulin. It is proposed a method to replace the daily repetitive injectable doses of insulin by a product oralyy administered. It is characterized by the following steps: a) mix at least a monomer suitable for polymerization by means of a ionizing radiation, with at least an aqueous solution of bioactive molecules; place the thus obtained mixture in step (a) into a resistant container permeable to said ionizing radiations; submit said container to a flow of ionizing radiation at a dose capable to polymerize all the monomer, in a dose range from 0.1 kGy up to 50 kGy, particularly in a 5 to 30 kGy in range, obtaining within the container a polymer resistant to the stomach acids. And the polymer containing in its nanotubules bioactive molecules; withdraw the thus polymer obtained in step (c), and dividing it in batches with a size range of 1 mm x 1 mm x 1 mm up to 8 mm x 8 mm x 8 mm, It is an objective of this invention. A method for the introduction of bioactive molecules in a polymeric substrate resistent to the stomach acids, to be employed as a retarding orally administered medicine, being these molecules insulin which is releaase directly to the liver being the liver its first action site, through the portal circulation; an orally relased insulin of delayed action by means of which, when the insulin is released into the liver, controls the porduction of hepatic glucose; an orally relased insulin of delayed action by means of which eht einsulin does not produce peaks in the systemic circulation, as it does with the injectable insulin, reducing the risks of the sudden descrese in the glucemia levels, an orally adminstered mediciene with a prolongued retared effect, by means of wish it is neccesary a lesser insulin dose.
Claims
1. Method for the inmobilization of bioactive molecules within a polymer substrate to be employed as an oral drug delivery system, comprising: a water insoluble but water swellable carrier matrix, incorporating the biologically active agents, where the matrix is a macromolecular network synthesized by gamma radiation at temperatures well below zero degree centigrade.
2. The method according to claim 1, where the polymer substrate is a hydrogel.
3. The method according to claim2, where the hydrogel is not biodegradable but it is biocompatible.
4. The method according to claim 1, where, initially before irradiation, DDSystem is an aqueous solution containing the bioactive molecules, mixed with the monomer components of the matrix and free radical scavengers.
5. The method according to claim 4, where the macromolecular network obtained after the radiation treatment is a porous substrate comprising a homopolymer or a copolymer prepared from one or more monomers selected from the group consisting of alkyl-methacrylates and acrylates.
6. The method according to claim 4, where the radiation treatment is from gamma radiation sources in a dose range from 0.1 kGy to SO kGy (kiloGray), particularly in a 5 to 30 kGy dose range.
7. The method according to claim 4 where the radiation treatment is from electron beams or bremsstrahlung( braking radiation) therefrom with energy between 0-1 MeV and 7 MeV
8. The method according to claim 7, in a dose range from 0.1 kGy to SO kGy (kiloGray), particularly in a 5 to 30 kGy dose range.
9. The method according to claim 1, where the temperature of the radiation treatments is well under freezing temperature, namely at glass state temperature.
10. The method according to claim4, where the bioactive molecule is insulin and the free radical scavengers is glycerin.
11. The polymer substrate according to claim 1, can be obtained in any shape and quantity and loaded with different amounts of bioactive molecules.
12. The polymer substrate according to claim 1, as a therapeutic-containing carrier can be subdivided and combined in different sizes containing each different amounts of the bioactive molecules.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US12/677,865 US8414923B2 (en) | 2007-09-13 | 2008-09-12 | Immobilization of bioactive molecules within a polymeric substrate |
| EP08807055A EP2200580A2 (en) | 2007-09-13 | 2008-09-12 | Method for the immobilization of bioactive molecules within a polymeric substrate resistant to the stomach acids as oral drug delivery system |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ARP070104071 | 2007-09-13 | ||
| ARP070104071A AR062846A1 (en) | 2007-09-13 | 2007-09-13 | METHOD FOR THE INCORPORATION OF BIOACTIVE MOLECULES IN A POLYMERIC SUBSTRATE RESISTANT TO STOMACH ACIDS, FOR ITS USE AS ORAL DELAYED RELEASE MEDICATION, PARTICULARLY INSULIN MOLECULES, AND THE MEDICINAL PRODUCT OBTAINED |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| WO2009034453A2 WO2009034453A2 (en) | 2009-03-19 |
| WO2009034453A3 WO2009034453A3 (en) | 2010-01-14 |
| WO2009034453A4 true WO2009034453A4 (en) | 2010-04-29 |
Family
ID=40225125
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/IB2008/002368 WO2009034453A2 (en) | 2007-09-13 | 2008-09-12 | Method for the immobilization of bioactive molecules within a polymeric substrate resistant to the stomach acids, to be employed as an oral drug delivery system, particularly insulin molecules, and medication so obtained |
Country Status (4)
| Country | Link |
|---|---|
| US (1) | US8414923B2 (en) |
| EP (1) | EP2200580A2 (en) |
| AR (1) | AR062846A1 (en) |
| WO (1) | WO2009034453A2 (en) |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH02212416A (en) * | 1988-12-22 | 1990-08-23 | Monsanto Co | Oral sending system for controlling medical inbibition |
| US6004583A (en) * | 1995-03-22 | 1999-12-21 | Orex Pharmaceutical Development Corp. | Protein-containing polymer composition for oral administration |
| US8128952B2 (en) * | 2005-01-12 | 2012-03-06 | Clemson University Research Foundation | Ligand-mediated controlled drug delivery |
-
2007
- 2007-09-13 AR ARP070104071A patent/AR062846A1/en active IP Right Grant
-
2008
- 2008-09-12 US US12/677,865 patent/US8414923B2/en not_active Expired - Fee Related
- 2008-09-12 WO PCT/IB2008/002368 patent/WO2009034453A2/en active Application Filing
- 2008-09-12 EP EP08807055A patent/EP2200580A2/en not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| WO2009034453A3 (en) | 2010-01-14 |
| US20110217378A1 (en) | 2011-09-08 |
| AR062846A1 (en) | 2008-12-10 |
| WO2009034453A2 (en) | 2009-03-19 |
| US8414923B2 (en) | 2013-04-09 |
| EP2200580A2 (en) | 2010-06-30 |
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